The specific aims of the project are to detect distinctive antibiotic resistance plasmids in bacterial isolates from one or more centers, trace their distribution and changes in distribution over time and relate this deployment to factors in their environment and alterations in their genetic structure. The methodology is to exploit a large existing base of data on quantitative antibiotic susceptibility test results from multiple centers, and to use existing computer programs which are able to detect distinctive antibiotypes produced by one or a small number of plasmids. Plasmids from representative isolates with the antibiotype are extracted and their structures compared by endonuclease restriction digestion analysis. When a correlation between plasmid structure and quantitative antibiotype is established, the epidemiology of the plasmid is traced and analyzed. Selected significant plasmids will be mapped to permit interpretation of structural or of functional variants. The project seeks to link the now advanced understanding of plasmid molecular structure with important issues of clinical antibiotic use through the complex epidemiology of antibiotic resistance plasmids, which connects the two subjects but for which there are now only fragmentary observations.